Targeted cancer therapy: giving histone deacetylase inhibitors all they need to succeed

Future Med Chem. 2012 Mar;4(4):505-24. doi: 10.4155/fmc.12.3.


Histone deacetylase inhibitors (HDACis) have now emerged as a powerful new class of small-molecule therapeutics acting through the regulation of the acetylation states of histone proteins (a form of epigenetic modulation) and other non-histone protein targets. Over 490 clinical trials have been initiated in the last 10 years, culminating in the approval of two structurally distinct HDACis - SAHA (vorinostat, Zolinza™) and FK228 (romidepsin, Istodax™). However, the current HDACis have serious limitations, including ineffectively low concentrations in solid tumors and cardiac toxicity, which is hindering their progress in the clinic. Herein, we review the primary paradigms being pursued to overcome these hindrances, including HDAC isoform selectivity, localized administration, and targeting cap groups to achieve selective tissue and cell type distribution.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Agents / toxicity
  • Chromatin / drug effects
  • Chromatin / metabolism
  • Clinical Trials as Topic
  • Histone Deacetylase Inhibitors / pharmacology
  • Histone Deacetylase Inhibitors / therapeutic use*
  • Histone Deacetylase Inhibitors / toxicity
  • Histone Deacetylases / chemistry
  • Histone Deacetylases / metabolism
  • Humans
  • Neoplasms / drug therapy*
  • Protein Isoforms / antagonists & inhibitors
  • Protein Isoforms / metabolism


  • Antineoplastic Agents
  • Chromatin
  • Histone Deacetylase Inhibitors
  • Protein Isoforms
  • Histone Deacetylases